Treatment

OBJECTIVES: In recent years, adjunctive therapies for epilepsy management are being explored due to considerable side effects carried by antiepileptic drugs (AEDs) and widespread reports of drug-resistant epilepsy. One such approach is non-invasive musical neurostimulation. Within this context, Mozart's sonata K448 has received particular attention following reports of reduced seizure frequency and a decrease in epileptiform discharges during and after music exposure; often described as the 'Mozart effect'...

BACKGROUND: PNPLA3 is a promising target for the treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease. ARO-PNPLA3 is a drug that efficiently lowers PNPLA3 expression in hepatocytes at the mRNA level, resulting in a significant reduction in liver fat in Phase I clinical trials. However, the long-term effects and potential side effects of ARO-PNPLA3 are not well understood. METHODS: We conducted a two-sample, two-step Mendelian randomization (MR) analysis to investigate the association between PNPLA3 inhibition and 10 cardiovascular diseases (CVDs), as well as the role of lipid traits as mediators...

AIMS: This study seeks to investigate ADHD symptoms and impulsivity among individuals diagnosed with Opioid Use Disorder (OUD) who also exhibit symptoms of Problematic Internet Use (PIU). METHODS: The study involved the participation of 360 Opioid Use Disorder (OUD) patients enrolled at an Alcohol and Drug Addiction Treatment Center (ADATC) during the period from October to December 2022. Various assessment tools were administered, including Young's Internet Addiction Scale (YIAS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Barratt Impulsiveness Scale (BIS), and Adult ADHD Self-Report Scale (ASRS)...

BACKGROUND: In the global strategy to eliminate leprosy, there remains a need for early case detection to successfully interrupt transmissions. Poor knowledge about leprosy and leprosy-related stigma are key drivers of delayed diagnosis and treatment. Sensitization campaigns to inform and increase awareness among the general population are an integral part of many national neglected tropical disease programs. Despite their importance, the effectiveness of such campaigns has not been rigorously studied in the West African context...

BACKGROUND: Disability is associated with alcohol misuse and drug overdose death, however, its association with alcohol-induced death remains understudied. OBJECTIVE: To quantify the risk of alcohol-induced death among adults with different types of disabilities in a nationally representative longitudinal sample of US adults. METHODS: Persons with disabilities were identified among participants ages 18 or older in the Mortality Disparities in American Communities (MDAC) study ( n  = 3,324,000)...

Introduction : Research indicates that take-home naloxone (THN) is saving lives across rural Appalachia, but whether it also results in treatment for opioid use disorders (OUDs) remains unclear. This study involves a detailed qualitative analysis of interviews with 16 individuals who had overdosed on opioids 61 times to understand why a THN intervention does not routinely lead to OUD treatment. Methods : This study builds upon a one-year (2018) qualitative study on community responses to opioid overdose fatalities in four adjacent rural counties in Western Pennsylvania...

Background: Facial muscle dysfunction can have drastic psychosocial effects. Objectives: To evaluate the impacts of customized neuromuscular retraining on mental health, quality of life (QoL), facial muscle function, and synkinesis. Methods: Thirty patients with facial nerve dysfunction completed a course of neuromuscular retraining. Patients' mental health, QoL, facial muscle function, and synkinesis were evaluated using Patient Health Questionnaire (PHQ-9), Facial Clinimetric Evaluation (FaCE) scale, electronic, clinician-graded facial function scale (eFACE), and Synkinesis Assessment Questionnaire (SAQ) at the initial and final visits...

PURPOSE: Identification of patients' intended chemotherapy regimens is critical to most research questions conducted in the real-world setting of cancer care. Yet, these data are not routinely available in electronic health records (EHRs) at the specificity required to address these questions. We developed a methodology to identify patients' intended regimens from EHR data in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study. METHODS: In women older than 18 years, diagnosed with primary stage I-IIIA breast cancer at Kaiser Permanente Northern California (2006-2019), we categorized participants into 24 drug combinations described in National Comprehensive Cancer Network guidelines for breast cancer treatment...

PURPOSE: To understand the mutational landscape of circulating tumor DNA (ctDNA) and tumor tissue of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) treated with abemaciclib + endocrine therapy (ET). METHODS: Blood samples for ctDNA and/or tissue samples were collected from abemaciclib-treated patients with HR+/HER2- MBC enrolled in the SCRUM-Japan MONSTAR-SCREEN project. Blood samples were collected before abemaciclib initiation (baseline) and at disease progression/abemaciclib discontinuation (post abemaciclib treatment)...

PURPOSE: Few studies have explored the potential for pharmacological interventions to delay disease progression in patients undergoing active surveillance (AS). This preplanned transcriptomic analysis of patient samples from the ENACT trial aims to identify biomarkers in patients on AS who are at increased risk for disease progression or who may derive the greatest benefit from enzalutamide treatment. PATIENTS AND METHODS: In the phase II ENACT (ClinicalTrials.gov identifier: NCT02799745) trial, patients on AS were randomly assigned 1:1 to 160 mg orally once daily enzalutamide monotherapy or continued AS for 1 year...

We prospectively analyzed clinical and laboratory characteristics associated with cardiac involvement and severe presentation in multisystem inflammatory syndrome in children. Of 146 patients, 66 (45.2%) had cardiac dysfunction and 26 (17.8%) had coronary artery abnormalities. Lower serum albumin levels, absolute lymphocyte and platelet counts, and elevated ferritin, fibrinogen, d-dimer and interleukin-6 levels were associated with cardiac dysfunction. Possible treatment complications were identified.

Bronchopleural fistula (BPF) is a potentially fatal complication and remains a surgical challenge. Concomitant problems, such as pulmonary infection and respiratory failure, are typically the main contributors to mortality from BPF because of improper contact between the bronchial and pleural cavity. We present the case of a 75-year-old male patient with a history of right upper lobe lung cancer resection who developed complex BPFs. Following appropriate antibiotic therapy and chest tube drainage, we treated the fistulas using endobronchial valve EBV placement and local argon gas spray stimulation...

TIGIT is an inhibitory receptor on immune cells that outcompetes an activating receptor, CD226, for shared ligands. Tumor-infiltrating lymphocytes express TIGIT and CD226 on regulatory T cells (Treg) and on CD8+ T cells with tumor-reactive or exhausted phenotypes, supporting the potential of therapeutically targeting TIGIT to enhance anti-tumor immunity. To optimize the efficacy of therapeutic antibodies against TIGIT, it is necessary to understand whether there is therapeutic benefit from Fcγ receptor (FcγR) binding...

OBJECTIVE: We established an orthopedic ward fracture liaison services (OWFLS) model and evaluated its role in improving detection rates of bone metabolic markers, treatment rates, and long-term treatability. METHODS: This observational retrospective cohort study included 120 patients aged >50 years hospitalized for primary osteoporotic fracture from January 2018 to January 2019 (group A: not included in OWFLS). Group B (included in OWFLS) comprised 120 patients from February 2019 to February 2020...

Ovarian cancer is a common tumor among women. It is often asymptomatic in the early stages, with most cases already at stage III to IVE at the time of diagnosis. Direct spread and lymphatic metastasis are the primary modes of metastasis, whereas hematogenous spread is rare. An initial diagnosis of ovarian cancer that has metastasized to the stomach is also uncommon. Therefore, clear treatment methods and prognostic data for such metastasis are lacking. In our hospital, we encountered a patient with an initial imaging diagnosis of a gastric tumor and a history of an ovarian tumor with endoscopic abdominal metastasis...

Pregabalin is the first-line treatment for neuropathic pain. Cases of cutaneous hypersensitivity reactions caused by pregabalin generally occur within 2 weeks of initiating medication. We report a rare case of a delayed cutaneous hypersensitivity reaction caused by pregabalin, which was confirmed by a drug provocation test. A 72-year-old man with severe herpes zoster neuralgia developed maculopapular drug eruption covering 80% to 90% of his total body surface area after 40 days of combined multidrug analgesia...

Metabolic subtypes of glioblastoma have different prognoses and responses to treatment. Deuterium metabolic imaging with 2H-labeled substrates is a potential approach to stratify patients into metabolic subtypes for targeted treatment. Here, we used 2H magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) measurements of [6,6'-2H2]glucose metabolism to identify metabolic subtypes and their responses to chemoradiotherapy in patient-derived glioblastoma xenografts in vivo. The metabolism of patient-derived cells was first characterized in vitro by measuring the oxygen consumption rate, a marker of mitochondrial TCA cycle activity, as well as the extracellular acidification rate and 2H-labeled lactate production from [6,6'-2H2]glucose, which are markers of glycolytic activity...

BACKGROUND: Inflammatory bowel diseases (IBDs) pose a significant challenge due to their diverse, often debilitating, and unpredictable clinical manifestations. The absence of prognostic tools to anticipate the future complications that require therapy intensification presents a substantial burden to patient private life and health. We aimed to explore whether the gut microbiome is a potential biomarker for future therapy intensification in a cohort of 90 IBD patients. METHODS: We conducted whole-genome metagenomics sequencing on fecal samples from these patients, allowing us to profile the taxonomic and functional composition of their gut microbiomes...

Although the selective and effective clearance of senescent cancer cells can improve cancer treatment, their development is confronted by many challenges. As part of efforts designed to overcome these problems, prodrugs, whose design is based on senescence-associated β-galactosidase (SA-β-gal), have been developed to selectively eliminate senescent cells. However, chemotherapies relying on targeted molecular inhibitors as senolytic drugs can induce drug resistance. In the current investigation, we devised a new strategy for selective degradation of target proteins in senescent cancer cells that utilizes a prodrug composed of the SA-β-gal substrate galactose (galacto) and the proteolysis-targeting chimeras (PROTACs) as senolytic agents...

BACKGROUND: Diagnostic reasoning is a complex cognitive process that requires intuitive, heuristic processing from knowledge and experience, as well as deliberate and reflective thinking. Evidence on interventions to improve diagnostic reasoning is inconsistent, in part because different terms and models are used to guide research. PURPOSE: To present a model of the factors of diagnostic reasoning in Advanced Practice Registered Nurses (APRNs), based on a review of the literature supporting the Metacognitive Diagnostic Reasoning (MDR) Model©...